Pyridine derivatives, derived from beta-ionone



Patented July 12, 194

2,47 5,.i29 V PYBID NE neswA s. PEM P ,e-IoNo g David Adriaan van Born and Jllsef Feltdinand Arens, Oss, Netherlands, assigngrs to qr; ganon, Oss, Netherlands, a

No Drawing. Application February 19 16, ;Serial No. 645,700. In the "Ngmer ane Septemher 7 945 6 Claims. (Cl.

1 This invention relates to certain pyridine derivatives derived from ,B-ionpne which are characterized by the general formula in which Pyr stands for a roup from the class consisting of the pyridyl roup ,CSHiN and the methylpyridyl group CHa-CsHsN and to the compounds, which may be obtained from the compounds stated above by splitting off one molecule of water and which are characterized by the general formula in which Pyr has the samemeaning as above.

These new compounds are obtained by reacting fl-ionone with a methylated pyridine derivative of the general iormula .GHsPyr, in which Pyr tands for a group selected ir n; the c ass consistin o the pyridyl group CEvH IN and the methylpyridyl group CHs-CsHsN. From the compounds of the general Formula I which are obtained as a product of this reaction water may be split oif, resulting in the production of compounds with the general Formula II.

The reaction between fl-ionone and the pyridine derivative may be brought about by reacting the components under the catalytic influence of zinc chloride pr some other catalyst acting in an analogous way. Another way of The tollowing examples may serve to l us: trate our inventi n. It is to be unde stq d O ever, that th invention is n t l mited hereto. but may be varied within the scope o h app nded claims.

fit-" mpl -a cm qii t 9f 1 4 7??? wi h were i is a emai ed; PJFPWQfiQ w th manger lea-. st n -r droppiilg i l l r ex ce qn er ga m1. t b 1 r laced y Pure El' e a @9- I -Q se he are 1,. a Qt .tiei saal pisses are newere f Heeldis ll d ma aw there es d flre alliedat igh speed, the nest em real that th efihef i the flask lgeeps boiling gently. After all' has been added, the stirring is continued for half an hour. The lithium then must be completely dissolved. vNow in five minutes a mixture of 10 g. of a-picoline and 5 cc. of abs. ether is added dropwise'. The solution is coloured dark yellow. After ten minutes to the ethereal solution of picolyl lithium which is obtained in this way a mixture of 9 g. ,of g-ionon e and 10 cc. of abs. ether is added dropwise'in about ten minutes. After refluxing for another half hour the mixture is left at room temperature for an hour. Then the darlg brown liquid is 'poured out on ice, at which the iarlccolour disappears at once. The ether layer is agitated with 'an excess of icecold 1 n. hydrochloricacid. The picolylionone passes over into the aqueous liquid. The water layer is washed with ether, then made slightly alkaline. The mixture is extracted with ether, the ether laye'ris washed, dried and distilled in high vacuum.

8 g. of picolylionone is obtained It is a pale yellow, viscous oil which distillsfjat a pressure of 0.001 m. m. between 135 and 1'42 C. Ons'tanding the oil slowly crystallizes. The melting point is l1-4=6"f('3. after pressing out ,on filter paper.

By heating at 7, 0 C. of 5 gfof the picolylionone with g. of finely powdered anhydrous oxalic acid ,during' 3 hours in 'an atmosphere of carbon dioxide arrhydro-picolylionone is obtained. The reaction product isQagitated with an excess of caustic soda, the remaining oil is taken up into ether, washed, 'dried and distilled. The fraction that boils above .C. .(0.01 m. m.) is taken up into ethanol and treated with an excess of a solution of pic ric acid/in ethanol. The picrate of 'anhydroj-picolylionqne which crystallizes is purified by recrystallisation from ethanol. Pale yellow crystalplates are obtained, melting at Q (corn). The recover'ed base is a thick 93' thi. m ra r 13 ene 15 Example 2.Condensation of p-ionone with 2,4- dimethylpyridine (lutidine) In an analogous way as described in Example 1 from 7.4 g. of lithium, 300 cc. of absolute ether and a mixture of 86.6 g. of bromobenzene with 90 cc, of ether a solution of phenyl lithium is prepared. A mixture of 61 cc. of freshly distilled 2,4-dimethylpyridine and 60 cc. of ether is added dropwise. After ten minutes a mixture of 60 g. of B-ionone and 60 cc. of ether is slowly added, while cooling in ice. The reaction mixture is left at room temperature for 1 hours, after which it is further treated as described in Example 1. The yield is 80 g. of lutidylionone, boiling at 136-143 C./0.001 m. m. It likewise crystallizes and melts at 44-51 C. When tested biologically it shows analeptic properties.

With the aim of preparing anhydro-lutidylionone a mixture of g. of lutidylionone and 16 g. of powdered anhydrous oxalic acid is heated in a vacuum of 1 m. m. in an oil bath, which is kept at 110 C. for half an hour. After that the mass is kept at 80 C. for another hour, After working up as described in Example 1 5.9 g. of anhydro-lutidylionone is obtained as a yellow oil, boiling at 140-147 C. under a pressure of 0.01 m. 111. After treatment with plcric acid two picrates may be obtained: a pale yellow picrate, melting at 166 C. (corn), which forms the chief product, and a dark yellow picrate, melting at 156 C. (corn), The two picrates are derived from two isomeric anhydro-lutidylionones, having the following structural formulas:

CHI

OH; on,

OCH=CH=CH-(B o-cH, N

Picrate M. P. 166 0.

ll /CE H2 What we claim is: 1. The compound in which Pyr stands for a group selected from the class consisting of the u-pyridyl group the -methyl -pyridyl group HC CH ts the 'y-pyridyl group and the u-methyl-v-pyridyl group 4. The process of preparing compounds of the general formula R -0H,-P r

in which R stands for the group CH: CH;

m0 C--CH=CH- Hi CH;

and Pyr stands for a group selected from the class consisting of the a-pyridyl group the Y-methyl a-pyridyl group 110 CH tn the -y-pyridyl group 30 \(IJH Ht a and the a-methyl v-pyridyl group 5. The process of preparing a compound of the formula ll CH on; 110 R-(E-CHw according to claim 4 which consists of reacting fl-ionone with .a lithium derivative or a-picoline, decomposing the reaction product with an aqueous liquid and isolating the resulting compound.

6. The process of preparing a mixture of compounds of the formula according to claim 4 which consists of reacting fl-ionone with a lithium derivative of 2,4-dimethyl pyridine, decomposing the reaction product with an aqueous liquid and isolating the resulting mixture.

DAVID ADRIAAN VAN DORP.

J OSEF FERDINAND ARENS.

REFERENCES CITED The following references are of record in the file of this patent:

Maier, Das pyridine und seiner derivatives, p. 44, 31 (1934).

Feiser, Organic Chemistry, 1944, page 1000. 

